Drosophila melanogaster and rodents show similar locomotor responses when exposed to cocaine. Previous work shows that the central circadian genes of Drosophila modulate cocaine responsiveness. The proposed experiments will determine how the circadian genes modulate cocaine responsiveness and in which cells of the adult brain these functions are required. I propose to identify the cells that modulate cocaine response and require the function of the clock protein PERIOD by transiently blocking synaptic function in various cells and determine the cocaine sensitivity phenotype. An overexpression screen in a sensitized period null background will be used to identify genes that modulate cocaine sensitivity. Subsequent experiments will determine whether the candidates are regulated, either directly or indirectly, by PERIOD function. Although the initial screens are for changes in cocaine sensitivity, it is expected that these pathways will be at least partially required for the process of sensitization.